Contributions of Different Cell Types to Spinal Muscular Atrophy Pathogenesis

Abstract Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease caused by the homozygous loss of survival motor neuron-1 (SMN1). While it is clear that SMA symptoms largely manifest as a motor neuron disease, a growing body of evidence strongly supports the notion that SMA is not a motor neuron cell autonomous disease, rather, that a variety of tissues and cell types contribute to the complex pathology. The nature of the non-motor neuron defects are complex and intertwined, and it is still unclear whether these SMN-associated deficiencies are cell autonomous. This chapter focuses mainly on the role of astrocytes and skeletal muscle as contributors to the complex SMA phenotype and the interplay between motor neurons, the central nervous system, and the periphery.